Buprenorphine is a long acting partial mu opioid agonist being developed as a maintenance treatment for opiod dependence. Buprenorphine attenuates the effects of challenge doses of opioids in humans, and this effect persists in a dose-related manner for periods up to 72 hours or longer. PET studies using [11C]carfentanyl (a high affinity, selective mu opiate receptor ligand) have found that buprenorhine produces dose related blockade of brain mu opioid receptors four hours after its administration. Pharmacokinetic studies have shown that buprenorphine administered sublingually reaches peak plasma levels in 90-120 minutes with a half-life of 12 hrs. The primary goal of this proposal is to compare the extent and time course of buprenorphine?s attenuation of the pharmacological effects of challenge doses of hydromorphone with its prevention of the binding of the mu opioid radiolabeled ligand, [11C]carfentanil, to brain mu receptors in opiate dependent participants. These effects will be examined at 4, 28, 52, and 76 hours after the last buprenorphine dose to determine if opioid blockade and mu opioid receptor binding decrease at comparable rates. Pharmacokinetic studies will also be conducted to determine the plasma levels of buprenorphine for comparison. We are hypothesizing that the magnitude of buprenorphine?s blockade of the pharmacological effects of hydromorphone is correlated with its leyel of mu opioid receptor binding. Secondly, we are hypothesizing that the rate of decline of the plasma levels of buprenorphine will be greater than the rate of decline of its binding to mu opioid receptors in the brain. This research will continue our exploration of the human pharmacology of buprenorphine as a prototypic opiate addiction treatment agent and serve to demonstrate the utility of pharmacodynamic, brain imaging and pharmacokinetic components of a multidimensional approach to the evaluation of new pharmacological treatment interventions.